Kinetics and Prediction of HBsAg Loss during Long-Term Therapy with Nucleos(t)ide Analogues of Different Potency in Patients with Chronic Hepatitis B

Background & Aims: About 350-400 million people are infected with hepatitis B virus (HBV) chronically and 1 million people die of hepatitis B virus (HBV)-related liver diseases. Nucleos(t)ide analogues (NAs) have been used for the treatment against HBV. However, few studies have investigated the long-term effects of different nucleos(t)ide analogues on levels of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB). The aims of this study were to measure the magnitude of HBsAg reduction by long-term monotherapy with adefovir dipivoxil (ADV) and entecavir (ETV), to compare HBsAg reduction between the two drugs of different potency and to predict the expected time needed to achieve HBsAg loss. Methods: We retrospectively evaluated the kinetics of HBsAg in 67 patients with CHB who all exhibited persistent viral suppression. These patients were treated with ADV or ETV for at least 6 years. HBV genotype was determined at baseline. Liver biochemistry, HBV serological markers, serum HBV DNA and HBsAg titers were determined at baseline, half year and yearly from year 1 to 6. Results: Serum HBsAg titers after treatment with ADV or ETV were significantly lower than the baseline titers (P<0.05). HBsAg reduction rate of patients treated with ETV (0.11 log(10) IU/mL/year) was higher than that treated with ADV (0.10 log(10) IU/mL/year), and the calculated expected time to HBsAg loss for patients treated with ETV (approximate 24.99 years) was shorter than that with ADV (approximate 30.33 years), but there was no statistically significant difference between two groups (P>0.05). Conclusion: Serum HBsAg titers gradually decreased during long-term treatment with either ADV or ETV. It appears that the potency of ADV on HBsAg reduction is close to that of ETV, as long as patients have achieved persistent viral suppression.